A mouse knockout library for secreted and transmembrane proteins

被引:278
作者
Tang, Tracy [1 ]
Li, Li [2 ]
Tang, Jerry [2 ]
Li, Yun [2 ]
Lin, Wei Yu [3 ]
Martin, Flavius [3 ]
Grant, Deanna [1 ]
Solloway, Mark [1 ]
Parker, Leon [4 ]
Ye, Weilan [4 ]
Forrest, William [5 ]
Ghilardi, Nico [1 ]
Oravecz, Tamas [6 ]
Platt, Kenneth A. [6 ]
Rice, Dennis S. [6 ]
Hansen, Gwenn M. [6 ]
Abuin, Alejandro [6 ]
Eberhart, Derek E. [6 ]
Godowski, Paul [3 ]
Holt, Kathleen H. [6 ]
Peterson, Andrew [1 ]
Zambrowicz, Brian P. [6 ]
de Sauvage, Frederic J. [1 ]
机构
[1] Genentech Inc, Dept Mol Biol, San Francisco, CA 94080 USA
[2] Genentech Inc, Bioinformat, San Francisco, CA 94080 USA
[3] Genentech Inc, Immunol, San Francisco, CA 94080 USA
[4] Genentech Inc, Tumor Biol & Angiogenesis, San Francisco, CA 94080 USA
[5] Genentech Inc, Nonclin Biostat, San Francisco, CA 94080 USA
[6] Lexicon Pharmaceut Inc, The Woodlands, TX USA
关键词
MUTAGENESIS; MICE; IDENTIFY; GENES; MODEL;
D O I
10.1038/nbt.1644
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Large collections of knockout organisms facilitate the elucidation of gene functions. Here we used retroviral insertion or homologous recombination to disrupt 472 genes encoding secreted and membrane proteins in mice, providing a resource for studying a large fraction of this important class of drug target. The knockout mice were subjected to a systematic phenotypic screen designed to uncover alterations in embryonic development, metabolism, the immune system, the nervous system and the cardiovascular system. The majority of knockout lines exhibited altered phenotypes in at least one of these therapeutic areas. To our knowledge, a comprehensive phenotypic assessment of a large number of mouse mutants generated by a gene-specific approach has not been described previously.
引用
收藏
页码:749 / U149
页数:9
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